System and method to control a non-paresthesia stimulation based on sensory action potentials

ABSTRACT

A system and method for controlling non-paresthesia stimulation of neural tissue of a patient. The method delivers a non-paresthesia stimulation waveform, senses sensory action potential (SAP) signals from the neural tissue of interest and analyzes the SAP signals to obtain SAP activity data for at least one of an SAP C-fiber component or an SAP A-delta fiber component. The method determines whether the SAP activity data satisfies a criteria of interest and adjusts at least one of the therapy parameters to change the non-paresthesia stimulation waveform when the SAP activity data does not satisfy the criteria of interest.

RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.15/944,806, filed Apr. 3, 2018 (now U.S. Pat. No. 10,272,250), which isa continuation of U.S. patent application Ser. No. 15/470,223, filedMar. 27, 2017 (now U.S. Pat. No. 9,931,510), entitled “SYSTEM AND METHODTO CONTROL A NON-PARESTHESIA STIMULATION BASED ON SENSORY ACTIONPOTENTIALS,” which is a continuation of U.S. patent application Ser. No.14/539,802, filed Nov. 12, 2014 (now U.S. Pat. No. 9,610,448), entitled“SYSTEM AND METHOD TO CONTROL A NON-PARESTHESIA STIMULATION BASED ONSENSORY ACT/ON POTENTIALS,” which are incorporated herein by reference.

BACKGROUND OF THE INVENTION

Spinal cord stimulation (SCS) is used to treat a wide range of chronicneuropathic pain conditions by delivering electrical stimulation toselect portions of the spinal cord. In the past, SCS therapy has beenproposed in which a tonic therapy is defined by single pulses have aselect pulse width, frequency and intensity. By way of example, tonictherapies have been proposed to manage cervical and lumbar pain. Thepulse width, frequency and intensity may be changed, along withelectrode configuration and placement on the spinal column in connectionwith pain relief for individual patients.

NS systems are devices that generate electrical pulses and deliver thepulses to nervous tissue to treat a variety of disorders. For example,spinal cord stimulation has been used to treat chronic and intractablepain. Another example is deep brain stimulation, which has been used totreat movement disorders such as Parkinson's disease and affectivedisorders such as depression. While a precise understanding of theinteraction between the applied electrical energy and the nervous tissueis not fully appreciated, it is known that application of electricalpulses to certain regions or areas of nervous tissue can effectivelyreduce the number of pain signals that reach the brain. For example,applying electrical energy to the spinal cord associated with regions ofthe body afflicted with chronic pain can induce “paresthesia” (asubjective sensation of numbness or tingling) in the afflicted bodilyregions.

SCS therapy, delivered via epidurally implanted electrodes, is a widelyused treatment for chronic intractable neuropathic pain of differentorigins. Traditional tonic therapy evokes paresthesia covering painfulareas of a patient During SCS therapy calibration, the paresthesia isidentified and localized to the painful areas by the patient inconnection with determining correct electrode placement.

Recently, new stimulation configurations such as burst stimulation andhigh frequency stimulation, have been developed, in which closely spacedhigh frequency pulses are delivered to the spinal cord in a manner thatdoes not generate paresthesias for the majority of patients, but stillaffords a therapeutic result. Neuropathic pain may result from lesionsor diseases affecting the peripheral or central regions of thesomatosensory system and is difficult to treat. The first spinal cordstimulator as a treatment for neuropathic pain was implanted by Shealyin 1967, which was based on the gate-control theory proposed by Melzackand Wall (1965). The gate-control theory proposed that the activation oflarge diameter A-beta (Aβ) fibers inhibits the transmission of noxiousstimuli to the brain via an inhibitory interneuron. It has been shownthat electrical stimulation also may activate these large A-beta fiberswith the same result. The A-beta fibers transmit information from theperiphery through the dorsal root ganglion (DRG) before projectingthrough the dorsal column.

Other types of sensory neurons (nerve cells) transmit information fromthe periphery through the DRG and terminate directly into the dorsalhorn of the spinal cord. A-delta (A-delta) fibers are small lightlymyelinated fibers that transmit mechanical or painful information, andmay be perceived as the sharp pain felt after injury. C-fibers are thesmallest and unmyelinated sensory neurons that transmit painfulinformation to spinothalamic tract neurons (major pain pathway) in thedorsal horn and may be perceived as the dull ache after injury.

Currently, there has been no way to determine values for the therapyparameters that define burst and other high frequency waveformstimulation without first inducing paresthesias through delivery oftonic waveform stimulation.

SUMMARY

In accordance with one embodiment, a method is provided for controllingnon-paresthesia stimulation of nervous tissue of a patient. The methodcomprises delivering a non-paresthesia stimulation waveform to at leastone electrode located proximate to nervous tissue of interest, thenon-paresthesia stimulation waveform including a series of pulsesconfigured to excite at least one of A-delta fibers or C-fibers of thenerve tissue of interest. The non-paresthesia stimulation waveform isdefined by therapy parameters. The method comprises sensing sensoryaction potential (SAP) signals from the nervous tissue of interest andanalyzing the SAP signals to obtain activity data for at least one of anSAP C-fiber component or an SAP A-delta fiber component. The method alsocomprises determining whether the activity data satisfies the criteriaof interest and adjusting at least one of the therapy parameters tochange the non-paresthesia stimulation waveform when the activity datadoes not satisfy the criteria of interest.

Optionally, the therapy parameters may define at least one of a burststimulation waveform or a high frequency stimulation waveform.Optionally, a determining operation may include determining whether ahigh frequency content of the SAP signal falls below a threshold orwithin an acceptable range, thereby indicating that no pain or anacceptable low level of pain is experienced by the patient. Optionally,the method may comprise a determining operation which includes analyzinga pain-activity data relation to identify a pain score, thepain-activity data relation corresponding to a relation between highfrequency content of the SAP signals and pain scores indicative of alevel of pain experienced by the patient.

Optionally, the method may further comprise iteratively repeating thedelivering, sensing and adjusting operations to optimize thenon-paresthesia stimulation waveform. Optionally, the method maycomprise an analyzing operation which includes analyzing a feature ofinterest from a morphology of the SAP signal over time, counting anumber of occurrences of the feature of interest that occur within theSAP signal over a predetermined duration, and generating the activitydata based on the number of occurrences of the feature of interest.

In accordance with an embodiment, a method is provided for controllingnon-paresthesia stimulation of nervous tissue of a patient. The methodcomprises providing a lead having at least one electrode on the leadconfigured to be implanted at a target position proximate to nervoustissue of interest. The method also comprises delivering anon-paresthesia stimulation waveform to the at least one electrode basedon a therapy parameter set (TPS), the stimulation waveform including aseries of pulses configured to excite at least one of A-delta fibers orC-fibers of the nervous tissue of interest. The method comprises sensingsensory action potential (SAP) signals, iteratively repeating thedelivering and sensing operations while changing at least one parameterfrom the TPS and analyzing the SAP signals to obtain activity dataassociated with the TPS for at least one of an SAP C-fiber component oran SAP A-delta fiber component. The analyzing operations obtain acollection of activity data associated with multiple therapy parameterset.

Optionally, the method further comprises selecting a candidate TPS fromthe multiple therapy parameter set, wherein the candidate TPS selectedhas corresponding activity data that meets a criteria of interest.Optionally, the method may include a selecting operation which includesoptimizing the candidate TPS to a stimulation configuration that affordsa result of interest without inducing paresthesia. Optionally, themethod may include an analyzing operation which identifies a highfrequency content of at least one of the SAP C-fiber component or theA-delta fiber component within the SAP signals sensed.

Optionally, the method may further comprise applying a reference noxiousinput during an interval between successive burst waveforms, thereference noxious input creating the SAP signals sensed. Optionally, themethod may further comprise changing at least one of the parameters forthe TPS during each iteration through the delivering, sensing andanalyzing operation. Optionally, the method may include the criteria ofinterest representing a number of peaks that occur in the SAP signal andthe candidate TPS selected has the fewest number of peaks with respectto the multiple therapy parameter sets analyzed. Optionally, the methodmay include the therapy parameters defining at least one of a burststimulation waveform or a high frequency stimulation waveform.

In accordance with another embodiment, a system is provided forcontrolling non-paresthesia stimulation of nervous tissue of a patient.The system comprises a lead having at least one stimulation electrode,the lead configured to be implanted at a target position proximate tonervous tissue of interest. The system also comprises an implantablepulse generator (IPG) coupled to the lead. The IPG is configured todeliver a stimulation waveform to at least one electrode based on atherapy parameter set (TPS), the stimulation waveform including a seriesof pulses configured to excite at least one of A-delta fibers orC-fibers of the nervous tissue. The IPG is coupled to a lead that sensessensory action potential (SAP) signals, and iteratively repeats thedelivering and sensing operations while changing at least one parameterfrom the TPS. The IPG analyzes the SAP signals to obtain activity dataassociated with the TPS for at least one of an SAP C-fiber component oran SAP A-delta fiber component, the analyzing operations obtaining acollection of activity data associated with multiple therapy parametersets (TPSs).

Optionally, the processor may be configured to select a candidate TPSfrom the multiple therapy parameter sets based on a criteria of interestrelated to the activity data, and utilize the candidate TPS inconnection with delivering non-paresthesia therapy. Optionally, thesystem may further comprise memory configured to store a pain-activitydata relation defining a relation between high frequency content of theSAP signals and pain scores indicative of pain experienced by a patient.Optionally, the system may include at least one electrode including amicroelectrode configured to be located immediately adjacent C-fibersand configured to sense a C-fiber sensory action potential (SAP)directly at the microelectrode.

Optionally, the processor may be configured to receive a pain scoreindicative of a level of pain experienced by the patient in connectionwith each of the therapy parameter sets, the processor configured todefine a relation between the activity data and the pain scores and savethe relation in memory. Optionally, the therapy parameters may define atleast one of a burst stimulation waveform or a high frequencystimulation waveform.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a neurostimulation system, according to an embodimentof the present disclosure.

FIGS. 2A-2C depict stimulation portions for inclusion at the distal endof lead.

FIG. 3A illustrates a process for collecting and analyzing activity datain connection with multiple therapy parameter sets in accordance withembodiments herein. FIG. 3B illustrates a process for collecting andanalyzing SAP signals to obtain SAP activity level data in connectionwith the operations of FIG. 3A in accordance with embodiments herein.

FIG. 3C illustrates a process for generating a correlation between painscores and activity data (e.g. high frequency content) in connectionwith multiple non-paresthesia therapies in accordance with embodimentsherein.

FIG. 3D illustrates a process for selecting a non-paresthesia therapy inaccordance with embodiments herein.

FIG. 4A illustrates an action potential measured from a C-fiber, withoutprior delivery of a non-paresthesia therapy in accordance withembodiments herein.

FIG. 4B illustrates an example plotting a relation between thenon-paresthesia therapy and the frequency of action potentials conveyedalong the C-fibers and/or A-delta fibers.

FIG. 4C illustrates an example plotting a relation between the frequencyof the action potential relative to a pain scale.

FIGS. 5A-5D illustrate examples of sensory action potential signalscollected in accordance with embodiments herein.

FIG. 6 illustrates a functional block diagram of an embodiment of anelectronic control unit that is operated in accordance with theprocesses described herein.

DETAILED DESCRIPTION

While multiple embodiments are described, still other embodiments of thedescribed subject matter will become apparent to those skilled in theart from the following detailed description and drawings, which show anddescribe illustrative embodiments of disclosed inventive subject matter.As will be realized, the inventive subject matter is capable ofmodifications in various aspects, all without departing from the spiritand scope of the described subject matter. Accordingly, the drawings anddetailed description are to be regarded as illustrative in nature andnot restrictive.

In accordance with embodiments herein, methods and systems are providedthat determine (e.g. optionally seek to optimize) alternativenon-paresthesia stimulation therapies, such as burst and high frequencystimulation waveforms, for neurostimulation systems (SCS, PNS, PNfS andDRG stimulation) that do not invoke paresthesias, while still affordingthe ability to suppress the pain by stimulation leads placed epidurallyor in other areas. The methods and systems determine non-paresthesiatherapies based on A-delta and C-fiber sensory action potentials (SAP)sensed from the DRG or dorsal roots (DR). In accordance with embodimentsherein, closed loop neurostimulation systems and methods are providedthat sense the A-delta and C-fiber SAPs component from the DRG (or DR).One or more features of interest (e.g. frequency of SAP) from theA-delta and C-fiber SAP component are used as feedback to selectsettings for therapy parameters that define stimulation waveforms, suchas burst and high frequency stimulation waveforms, frequencies as wellas lead implant locations, thereby enabling both energy conservation andstimulation efficacy. The pain signals transmitted within A-delta and Cfibers are spontaneously generated action potentials that appear as“spikes” in the electrical signal measured at the electrodes. The morepain felt, the higher the SAP frequency or spike frequency of theA-delta and C-fibers. The methods and systems herein, seek to suppressor ameliorate pain related SAPs conveyed by the A-delta fibers and/orC-fibers.

Nervous System Overview

The nervous system is comprised of the central nervous system (CNS) andthe peripheral nervous system (PNS). The CNS contains the brain andspinal cord. The PNS is comprised mainly of mixed nerves, which areenclosed bundles of the long fibers or axons (endings of nerve cells orneurons) that connect the CNS to every other part of the body. There aretwo types of nerve fibers in a mixed nerve that include: sensory nervefibers (afferent fibers sending information towards the brain) and motornerve fibers (efferent fibers sending information from the brain).Sensory neurons transmit information from the environment, such as painand motor neurons that mediate voluntary and involuntary movement.

In general, the peripheral nerve fibers may be classified into threetypes of nerve fibers based on the nerve fiber diameter and conductionvelocity, namely A-, B- and C-fibers. A-fibers have large diameters,high conduction velocities, are highly myelinated, and are furthersubdivided by size and conduction velocity as A-alpha, A-beta, A-gammaand A-delta fibers. By way of example, the fast conduction velocity ofthe A-alpha fibers may be on the order of 80-120 m/s, and the A-alphafibers may be on average 13-20 μm in diameter. B-fibers have diametersof about 3 um and conduction velocities of 3-15 m/s. C-fibers are smallneurons with slow conduction velocities and are not myelinated.

A-delta fibers have conduction velocities on the order of 5-35 m/s, andthe A-delta fibers may be on average 1.0-5.0 μm in diameter. A-deltafibers carry information mainly from the nociceptive-mechanical ormechanothermal-specific stimuli and are considered nociceptors. Theirreceptive fields (area of innervation) are small, and therefore, provideprecise localization of pain.

C-fibers are unmyelinated, have a small diameter and low conductionvelocity. By way of example, the slow conduction velocity of theC-fibers may be on the order of 0.5-2.0 m/s, and the C-fibers may be onaverage 0.2-1.5 μm in diameter. C-fibers carry sensory information, suchas nociception (pain), temperature, and itch. C-fibers are unmyelinatedunlike most other fibers in the nervous system. The lack of myelinationis, at least in part, a cause of the slow conduction velocity attributedto C-fibers.

C-fibers are activated by and carry information from a variety ofhigh-intensity mechanical, chemical and thermal stimulation and thus areconsidered as polymodal nociceptors. C-fibers comprise about 70% of allthe fibers carrying noxious input. The receptive field of these neuronsis large and, therefore, less precise for pain localization.

The cell bodies of all primary afferent pain neurons from the body,face, and head are located in the dorsal root ganglia (DRG) and in thetrigeminal ganglia respectively. Some of these cell bodies havemyelinated axons (A-delta fibers), and others have unmyelinated axons(C-fibers). Both A-delta fiber's and the unmyelinated C-fiber's axonshave free nerve endings, which innervate the same areas in theperiphery.

A-delta fibers are responsible for the sensation of a quick shallow painthat is specific on one area, termed as first pain. The A-delta fibersrespond to a weaker intensity of noxious stimulus. C-fibers respond tonoxious stimuli which have stronger intensities and account for theslow, but deeper second pain that spreads out over an unspecific area.

Nociception is the response to painful stimuli transmitted via sensoryaction potentials of A-delta and C-fibers. SCS therapy may decrease thefrequency of the nociceptive action potentials with varying efficacy asthe therapy parameters change. Burst and high frequency type SCStherapies can be controlled by adjusting relevant parameters to modulatethe charge delivered to the spinal cord during stimulation. As explainedherein, the efficacy of burst and high frequency waveform stimulationsmay be dependent on certain therapy parameters, more so than othertherapy parameters (e.g. dependent on the charge per burst).

FIG. 4A illustrates an action potential measured from a C-fiber, withoutprior delivery of a non-paresthesia therapy. The vertical axisrepresents the voltage potential measured by the electrodes, and thehorizontal axis represents time. When an external input (e.g. pain)occurs at an area of interest on a patient, action potentials areconveyed along the C-fibers and A-delta fibers. Action potentialsinclude numerous peaks and valleys, generally referred to as spikes ordirection changes. The magnitude of the spikes/direction changes, aswell as the rate of occurrence (frequency) for the spikes/directionchanges, correlate with a severity of the external input (e.g. pain orpain scores that measured at clinics). In accordance with embodimentsherein, the magnitude and rate of occurrence of the spikes/directionchanges are suppressed when an appropriate non-paresthesia therapy isdelivered.

FIG. 4B illustrates an example plotting a relation between thenon-paresthesia therapy and the frequency of action potentials conveyedalong the C-fibers and/or A-delta fibers. The horizontal axiscorresponds to the energy (in milliamps) delivered from the leadelectrode by the non-paresthesia therapy. The vertical axis correspondsto a count of the number of spikes/direction changes (frequency) in theaction potential. As shown in FIG. 4B, as the energy level is increasedfrom 10 to 40 mA, the number of spikes in the action potentialdecreases.

FIG. 4C illustrates an example plotting a relation between the frequencyof the action potential relative to a pain scale measured. Thehorizontal axis corresponds to the frequency of the action potentialsconveyed along the C-fibers and/or A-delta fibers. The vertical axiscorresponds to the pain scale, which represents a visual analog scale,for which values are provided by a patient during testing. As explainedbelow in connection with FIGS. 3A-3D, after implant of an NS system 100,non-paresthesia therapy is delivered. The therapy parameters, definingburst or high frequency stimulation waveforms, may be varied (e.g.,number of burst, intervals, pulse duration, pulse amplitude etc., andlead implant locations) between each VAS or NRS rating. The highfrequency content of action potentials is identified from the SAPsignals in connection with each non-paresthesia therapy. In addition,the patient is asked to provide a pain score and the measured frequencyof the action potentials (AP) is correlated to the pain scores. Thepatient is requested to note his/her pain intensity score, e.g. visualanalog scale (VAS) or numeric rating scale (NRS) or based on anotherpain scale, in connection with each non-paresthesia therapy. FIG. 4Crepresents an example of how a patient's VAS may vary as a function ofthe frequency of AP. In the example of FIG. 4C, the function representsa linear relationship, such that the correlation coefficient is theslope of the curve and the unit is “pain score per μV”. Optionally, anon-linear relationship may be determined as the pain per unit measure.

In accordance with embodiments herein, a programmer is provided that isconfigured to select therapy parameters that define a non-paresthesiatherapy that achieves a desired result. After implantation of the NSsystem 100, an intraoperative programming session may be conducted whilethe patient remains under general or local anesthetic. The SAP signalsare recorded and visualized, such as on the clinician's programmer,patient programmer or an external device. The high frequency content ofAPs is then extracted from the SAP signals, converted to the VASaccording to the calibration test (e.g., of FIG. 3C), and is shown onthe programmer. Then the parameters of the alternative stimulation (suchas number of bursts, intervals, pulse duration, pulse amplitude, etc.)may be changed until the frequency of action potentials from A-delta andC fibers are reduced to a desired level, such as minimized or completelydisappear. During subsequent programming sessions, the frequency of APsfrom A-delta and C fibers may be monitored from the same recordingelectrode and compared to the “AP frequency” generated from “the maximaltolerant pain”, and thus, provide feedback to the NS system 100 tofurther change/optimize/control the stimulation parameters.

To determine a select placement of the SCS leads, the DRG and SCS leadsmay be placed into respective implant locations. The frequency of APsmay be measured from the A-delta and C fibers. The SCS stimulation leadmay be moved until a select placement is determined based on reductionof A-delta and C fiber APs (e.g., optional placement may correspond to amaximum reduction of APs).

In accordance with embodiments, for ambulatory monitoring, afterimplant, the NS system 100 stimulates the spinal cord or DRG for painrelief, while sampling measures of APs. The NS system 100 converts theAP measures to a pain score using a correlation coefficient (e.g. aspredefined in FIG. 4C) and saves the pain score to the memory of the NSsystem 100 for downloading later or sends to the network database fordiagnostic purpose by a pain physician. In an ambulatory state, the NSsystem 100 will record the AP from the leads after stimulation, comparethe frequency of APs associated with each pain scale, and change thestimulation levels until the frequency of APs detected are reduced by aselect amount (e.g., optimizing the stimulation output).

System Overview

FIG. 1 depicts an NS system 100 that generates electrical pulses forapplication to tissue of a patient according to one embodiment. Forexample, the NS system 100 may be adapted to stimulate spinal cordtissue, peripheral nervous tissue, deep brain tissue, cortical tissue,cardiac tissue, digestive tissue, pelvic floor tissue, or any othersuitable nervous tissue of interest within a patient's body.

The NS system 100 may be controlled to deliver various types ofnon-paresthesia therapy, such as high frequency neurostimulationtherapies, burst neurostimulation therapies and the like. High frequencyneurostimulation includes a continuous series of monophasic or biphasicpulses that are delivered at a predetermined frequency (such as 2-10K).Burst neurostimulation includes short sequences of monophasic orbiphasic pulses, where each sequence is separated by a quiescent period.By way of example, the pulses within each burst sequence may bedelivered with an intraburst frequency of about 500 Hz. In general,non-paresthesia therapies include a continuous, repeating orintermittent pulse sequence delivered at a frequency and amplitudeconfigured to avoid inducing (or introduce a very limited) paresthesia.

The NS system 100 may represent a closed loop neurostimulation device,where the new device is configured to provide real-time sensingfunctions for A-delta and C-fiber action potential (APs) from a dorsalroot ganglion (DRG) lead. The configuration of the lead sensingelectrodes that sense action potentials from the A-delta and C fibersmay be varied depending on the neuronal anatomy of the sensing site(s)of interest. The size and shape of electrodes is varied based on theimplant location, such as the dorsal root (DR) or DRG. By way of exampleonly, a laminectomy procedure may be used, in order to obtain accurateaction potential signals indicative of pain from the C fiber and/or theA-delta fiber. The electronic components within the NS system 100 aredesigned with both stimulation and sensing capabilities, includingalternative non-paresthesia stimulation therapy, such as burst mode,high frequency mode and the like. The NS system 100 detects A-delta andC-fiber action potentials from a patient's painful area and qualifyA-delta and C-fiber action potential signals based on a predeterminedpain scale. Changes to the frequency of the A-delta and C-fiber actionpotential signals is used to guide parameter settings for thenon-paresthesia stimulation therapy, such as to define burst or highfrequency parameters. In one embodiment, one lead stimulates the dorsalcolumn, the second lead senses from DRG or DR. In another embodiment,the lead can stimulate DRG or DR and sense from the same stimulationlocation.

The NS system 100 includes an implantable pulse generator (IPG) 150 thatis adapted to generate electrical pulses for application to tissue of apatient. The IPG 150 typically comprises a metallic housing or can 158that encloses a controller 151, pulse generating circuitry 152, acharging coil 153, a battery 154, a far-field and/or near fieldcommunication circuitry 155, battery charging circuitry 156, switchingcircuitry 157, memory 158 and the like. The controller 151 typicallyincludes a microcontroller or other suitable processor for controllingthe various other components of the device. Software code is typicallystored in memory of the IPG 150 for execution by the microcontroller orprocessor to control the various components of the device.

The IPG 150 may comprise a separate or an attached extension component170. If the extension component 170 is a separate component, theextension component 170 may connect with the “header” portion of the IPG150 as is known in the art. If the extension component 170 is integratedwith the IPG 150, internal electrical connections may be made throughrespective conductive components. Within the IPG 150, electrical pulsesare generated by the pulse generating circuitry 152 and are provided tothe switching circuitry 157. The switching circuitry 157 connects tooutputs of the IPG 150. Electrical connectors (e.g., “Bal-Seal”connectors) within the connector portion 171 of the extension component170 or within the IPG header may be employed to conduct variousstimulation pulses. The terminals of one or more leads 110 are insertedwithin connector portion 171 or within the IPG header for electricalconnection with respective connectors. Thereby, the pulses originatingfrom the IPG 150 are provided to the leads 110. The pulses are thenconducted through the conductors of the lead 110 and applied to tissueof a patient via stimulation electrodes 121 that are coupled to blockingcapacitors. Any suitable known or later developed design may be employedfor connector portion 171.

The stimulation electrodes 121 may be positioned along a horizontal axis102 of the lead 110 and are angularly positioned about the horizontalaxis 102 so the stimulation electrodes 121 do not overlap. Thestimulation electrodes 121 may be in the shape of a ring such that eachstimulation electrode 121 continuously covers the circumference of theexterior surface of the lead 110. Each of the stimulation electrodes 121are separated by non-conducting rings 112, which electrically isolateeach stimulation electrode 121 from an adjacent stimulation electrode121. The non-conducting rings 112 may include one or more insulativematerials and/or biocompatible materials to allow the lead 110 to beimplantable within the patient. Non-limiting examples of such materialsinclude polyimide, polyetheretherketone (PEEK), polyethyleneterephthalate (PET) film (also known as polyester or Mylar),polytetrafluoroethylene (PTFE) (e.g., Teflon), or parylene coating,polyether bloc amides, polyurethane. The stimulation electrodes 121 maybe configured to emit the pulses in an outward radial directionproximate to or within a stimulation target. Additionally, oralternatively, the stimulation electrodes 121 may be in the shape of asplit or non-continuous ring such that the pulse may be directed in anoutward radial direction adjacent to the stimulation electrodes 121. Thestimulation electrodes 121 deliver high frequency and/or burststimulation waveforms as described herein. The electrodes 121 may alsosense sensory action potential (SAP signals) for a data collectionwindow. Optionally, the delivering operation may deliver the onestimulation waveform to a first sub-set of the electrodes and anotherstimulation waveform to a second sub-set of the electrodes, where thefirst and second sub-sets have at least one unique electrode relative toeach other.

Optionally, the electrodes may include a microelectrode locatedimmediately adjacent C-fibers. The method may sense a C-fiber sensoryaction potential (SAP) directly at the microelectrode and perform aniterative feedback loop to adjust at least one therapy parameter basedon the A-delta or C-fiber SAP.

The lead 110 may comprise a lead body 172 of insulative material about aplurality of conductors within the material that extend from a proximalend of lead 110, proximate to the IPG 150, to its distal end. Theconductors electrically couple a plurality of the stimulation electrodes121 to a plurality of terminals (not shown) of the lead 110. Theterminals are adapted to receive electrical pulses and the stimulationelectrodes 121 are adapted to apply the pulses to the stimulation targetof the patient. Also, sensing of physiological signals may occur throughthe stimulation electrodes 121, the conductors, and the terminals. Itshould be noted that although the lead 110 is depicted with fourstimulation electrodes 121, the lead 110 may include any suitable numberof stimulation electrodes 121 (e.g., less than four, more than four) aswell as terminals, and internal conductors. Additionally, oralternatively, various sensors (e.g., a position detector, a radiopaquefiducial) may be located near the distal end of the lead 110 andelectrically coupled to terminals through conductors within the leadbody 172.

Although not required for any embodiments, the lead body 172 of the lead110 may be fabricated to flex and elongate upon implantation oradvancing within the tissue (e.g., nervous tissue) of the patienttowards the stimulation target and movements of the patient during orafter implantation. By fabricating the lead body 172, according to someembodiments, the lead body 172 or a portion thereof is capable ofelastic elongation under relatively low stretching forces. Also, afterremoval of the stretching force, the lead body 172 may be capable ofresuming its original length and profile. For example, the lead body maystretch 10%, 20%, 25%, 35%, or even up or above to 50% at forces ofabout 0.5, 1.0, and/or 2.0 pounds of stretching force. Fabricationtechniques and material characteristics for “body compliant” leads aredisclosed in greater detail in U.S. Provisional Patent Application No.60/788,518, entitled “Lead Body Manufacturing,” which is expresslyincorporated herein by reference.

FIGS. 2A-2C respectively depict stimulation portions 200, 225, and 250for inclusion at the distal end of lead 110. Stimulation portion 200depicts a conventional stimulation portion of a “percutaneous” lead withmultiple ring electrodes. Stimulation portion 225 depicts a stimulationportion including several segmented electrodes. Example fabricationprocesses are disclosed in U.S. patent application Ser. No. 12/895,096(now U.S. Pat. No. 9,054,436), entitled, “METHOD OF FABRICATINGSTIMULATION LEAD FOR APPLYING ELECTRICAL STIMULATION TO TISSUE OF APATIENT,” which is incorporated herein by reference. Stimulation portion250 includes multiple planar electrodes on a paddle structure. Returningto FIG. 1, for implementation of the components within the IPG 150, aprocessor and associated charge control circuitry for an IPG isdescribed in U.S. Pat. No. 7,571,007, entitled “SYSTEMS AND METHODS FORUSE IN PULSE GENERATION,” which is expressly incorporated herein byreference. Circuitry for recharging a rechargeable battery (e.g.,battery charging circuitry 156) of an IPG using inductive coupling andexternal charging circuits are described in U.S. Pat. No. 7,212,110,entitled “IMPLANTABLE DEVICE AND SYSTEM FOR WIRELESS COMMUNICATION,”which is expressly incorporated herein by reference.

An example and discussion of “constant current” pulse generatingcircuitry (e.g., pulse generating circuitry 152) is provided in U.S.Patent Publication No. 2006/0170486 entitled “PULSE GENERATOR HAVING ANEFFICIENT FRACTIONAL VOLTAGE CONVERTER AND METHOD OF USE,” which isexpressly incorporated herein by reference. One or multiple sets of suchcircuitry may be provided within the IPG 150. Different burst and/orhigh frequency pulses on different stimulation electrodes 121 may begenerated using a single set of the pulse generating circuitry 152 usingconsecutively generated pulses according to a “multi-stimset program” asis known in the art. Complex pulse parameters may be employed such asthose described in U.S. Pat. No. 7,228,179, entitled “Method andapparatus for providing complex tissue stimulation patterns,” andInternational Patent Publication Number WO 2001/093953 A1, entitled“NEUROMODULATION THERAPY SYSTEM,” which are expressly incorporatedherein by reference. Alternatively, multiple sets of such circuitry maybe employed to provide pulse patterns (e.g., tonic stimulation waveform,burst stimulation waveform) that include generated and deliveredstimulation pulses through various stimulation electrodes of one or moreleads 121 as is also known in the art. Various sets of parameters maydefine the pulse characteristics and pulse timing for the pulses appliedto the various stimulation electrodes 121. Although constant currentpulse generating circuitry is contemplated for some embodiments, anyother suitable type of pulse generating circuitry may be employed suchas constant voltage pulse generating circuitry.

The controller 151, among other things, comprises a lead having at leastone stimulation electrode, the lead configured to be implanted at atarget position proximate to nervous tissue of interest; and animplantable pulse generator (IPG) coupled to the lead. The controller151 delivers a non-paresthesia stimulation waveform to at least oneelectrode located proximate to nervous tissue of interest, thenon-paresthesia stimulation waveform including a series of pulsesconfigured to excite at least one of A-delta fibers or C-fibers of thenervous tissue of interest, the non-paresthesia stimulation waveformdefined by therapy parameters. The controller 151 senses sensory actionpotential (SAP) signals from at least one electrode on the lead. Thecontroller 151 analyzes the SAP signals to obtain activity data for atleast one of an SAP C-fiber component or an SAP A-delta fiber component.The controller 151 determines whether the activity data satisfies acriteria of interest. The controller 151 adjusts at least one of thetherapy parameters to change the non-paresthesia stimulation waveformwhen the activity data does not satisfy the criteria of interest.

The controller 151 iteratively repeats the delivering and sensingoperations for a group of TPS. The IPG analyzes the SAP signals toobtain activity data associated with the TPS for at least one of SAPC-fiber components or SAP A-delta fiber components, the analyzingoperations obtaining a collection of activity data associated with thegroup of TPS. The IPG selects a candidate TPS from the group of TPSbased on a criteria of interest.

The therapy parameters define at least one of a burst stimulationwaveform or a high frequency stimulation waveform. The controller 151may determine whether a high frequency content of the SAP signal failsbelow a threshold or within an acceptable range, thereby indicating thatno pain or an acceptable low level of pain is experienced by thepatient. The controller 151 may analyze a pain-activity data relation toidentify a pain score, the pain-activity data relation corresponding toa relation between high frequency content of the SAP signals and painscores indicative of a level of pain experienced by the patient. Thecontroller 151 repeats the delivering, sensing and adjusting operationsto optimize the non-paresthesia stimulation waveform. The analyzingoperation may include analyzing a feature of interest from a morphologyof the SAP signal over time, counting a number of occurrences of thefeature of interest that occur within the SAP signal over apredetermined duration, and generating the activity data based on thenumber of occurrences of the feature of interest.

The controller 151 is configured to select a candidate TPS from themultiple therapy parameter sets based on a criteria of interest relatedto the activity data, and utilize the candidate TPS in connection withdelivering non-paresthesia therapy. The controller 151 is configured toreceive a pain score indicative of a level of pain experienced by thepatient in connection with each of the therapy parameter sets. Thecontroller 151 is configured to define a relation between the activitydata and the pain scores and save the relation in memory. The therapyparameters define at least one of a burst stimulation waveform or a highfrequency stimulation waveform.

Optionally, the controller 151 may be configured wherein the leadincludes a plurality of electrodes, and the IPG is configured to deliverwherein the at least one electrode includes a microelectrode configuredto be located immediately adjacent C-fibers and configured to sense aC-fiber sensory action potential (SAP) directly at the microelectrode.Optionally, the controller 151 may be configured wherein the processoradjusts the TPS for the burst waveform based on the C-fiber SAPcomponent of the signals.

The controller 151 identifies a C-fiber and/or A-delta SAP components ofthe signals. The controller 151 further comprises comprising adjustingthe therapy parameters based on the C-fiber and/or A-delta SAPcomponents of the signals. The controller 151 adjusting operationincludes adjusting the burst frequency to reduce the C-fiber SAPcomponent. The controller 151 further comprises analyzing a feature ofinterest from a morphology of the C-fiber and/or A-delta SAP componentsover time, counting a number of occurrences of the feature of interestthat occur within the C-fiber and/or A-delta SAP components over apredetermined duration, comparing the number of occurrences to a priornumber of occurrences, and adjusting the parameter settings based on thecomparing operation.

Memory 158 stores software to control operation of the controller 151for coupled tonic/burst therapy as explained herein. The memory 158 alsostores SAP signals, therapy parameters, SAP activity level data, painscales and the like. For example, the memory 158 may save SAP activitylevel data for various different therapies as applied over a short orextended period of time. A collection of SAP activity level data isaccumulated for different therapies and may be compared to identifyhigh, low and acceptable amounts of sensory activity for the A-deltaand/or C-fibers that result from different therapies. The memory 158stores a pain-activity data relation defining a relation between highfrequency content of the SAP signals and pain scores indicative of painexperienced by a patient.

A controller device 160 may be implemented to charge/recharge thebattery 154 of the IPG 150 (although a separate recharging device couldalternatively be employed) and to program the IPG 150 on the pulsespecifications while implanted within the patient. Although, inalternative embodiments separate programmer devices may be employed forcharging and/or programming the NS system 100. The controller device 160may be a processor-based system that possesses wireless communicationcapabilities. Software may be stored within a non-transitory memory ofthe controller device 160, which may be executed by the processor tocontrol the various operations of the controller device 160. A “wand”165 may be electrically connected to the controller device 160 throughsuitable electrical connectors (not shown). The electrical connectorsmay be electrically connected to a telemetry component 166 (e.g.,inductor coil, RF transceiver) at the distal end of wand 165 throughrespective wires (not shown) allowing bi-directional communication withthe IPG 150. Optionally, in some embodiments, the wand 165 may compriseone or more temperature sensors for use during charging operations.

The user may initiate communication with the IPG 150 by placing the wand165 proximate to the NS system 100. Preferably, the placement of thewand 165 allows the telemetry system of the wand 165 to be aligned withthe far-field and/or near field communication circuitry 155 of the IPG150. The controller device 160 preferably provides one or more userinterfaces 168 (e.g., touchscreen, keyboard, mouse, buttons, or thelike) allowing the user to operate the IPG 150. The controller device160 may be controlled by the user (e.g., doctor, clinician) through theuser interface 168 allowing the user to interact with the IPG 150. Theuser interface 168 may permit the user to move electrical stimulationalong and/or across one or more of the lead(s) 110 using differentstimulation electrode 121 combinations, for example, as described inU.S. Patent Application Publication No. 2009/0326608, entitled “METHODOF ELECTRICALLY STIMULATING TISSUE OF A PATIENT BY SHIFTING A LOCUS OFSTIMULATION AND SYSTEM EMPLOYING THE SAME,” which is expresslyincorporated herein by reference.

Also, the controller device 160 may permit operation of the IPG 150according to one or more therapies to treat the patient. Each therapymay include one or more sets of stimulation parameters of the pulseincluding pulse amplitude, pulse width, pulse frequency or inter-pulseperiod, pulse repetition parameter (e.g., number of times for a givenpulse to be repeated for respective stimset during execution ofprogram), biphasic pulses, monophasic pulses, etc. The IPG 150 modifiesits internal parameters in response to the control signals from thecontroller device 160 to vary the stimulation characteristics of thestimulation pulses transmitted through the lead 110 to the tissue of thepatient. NS systems, stimsets, and multi-stimset programs are discussedin PCT Publication No. WO 2001/093953, entitled “NEUROMODULATION THERAPYSYSTEM,” and U.S. Pat. No. 7,228,179, entitled “METHOD AND APPARATUS FORPROVIDING COMPLEX TISSUE STIMULATION PATTERNS,” which are expresslyincorporated herein by reference.

FIGS. 3A-3D illustrate processes for controlling non-paresthesia (e.g.burst and/or high frequency) stimulation of nervous tissue of a patientin accordance with embodiments herein. The operations of FIGS. 3A-3D maybe implemented by one or more processors, such as within an implantablepulse generator, external programmer, another external device and thelike. The IPG, external programmer or other external device are coupledto a lead having at least one stimulation electrode that is implanted ata target position proximate to nervous tissue of interest.

FIG. 3A illustrates a process for collecting and analyzing activity datain connection with multiple therapy parameter sets in accordance withembodiments herein. At 302, the method defines one or morenon-paresthesia stimulation waveform to be used. The stimulationwaveform is defined by one or more parameters forming a therapyparameter set (TPS). Examples of therapy parameters within a TPSinclude, but are not limited to pulse amplitude, pulse width, interpulsedelay, number of pulses per burst, pulse frequency, burst frequency,etc. The TPS is defined such that the stimulation waveform is configuredto excite at least one of A-delta fibers and/or C-fibers at the targetposition. The TPS causes the stimulation waveform to exhibit amorphology that does not excite A-beta fibers at all or sufficiently toinduce notable paresthesia, also referred to as a non-A-beta fiberexcitation morphology.

At 304, the method senses SAP baseline signals by collecting SAPsignals, for a data collection window while no external input is appliedto the patient. The SAP baseline signals are indicative of the sensoryaction potential experienced naturally or inherently by nervous tissueof interest at the target position. The SAP baseline signals, collectedover a single data collection window, represent an SAP baseline samplefor a single time interval, where the SAP baseline sample is indicativeof a baseline responsiveness of the fibers of interest (C-fibers and/orA-delta fibers), such as when no external sensory stimulation isdelivered. For example, the baseline responsiveness may correspond to anabsence of external pitch, pressure, external temperature source, or anyother external input that would otherwise cause activity within thefibers of interest.

Throughout the embodiments described herein, the same electrodes may beused for sensing and stimulation. Alternatively, one group of electrodesmay be used for sensing, while a different group of electrodes are usedfor stimulation. For example, the sensing electrodes may be spaced apartalong the lead from the stimulation electrodes. Optionally, the sensingelectrodes may be provided on a separate lead unique and distinct fromthe lead that includes the stimulation electrodes. For example, aconventional SCS lead may be positioned along the spinal column at adesired location in order to deliver therapy at one or more stimulationsites of interest, while a separate sensing lead is provided. As oneexample, electrodes proximate the dorsal column may be used forstimulation, while separate electrodes proximate the dorsal rootganglion (DRG) or dorsal root (DR) are used for sensing. As a furtheroption, sensing electrodes may be located remote from the DRG or DR,such as within the torso of the body and/or along the extremities of thepatient, such as within the arms and legs. Optionally, the burststimulation waveform may be delivered at electrodes proximate both ofthe dorsal column and the DRG, while sensing is performed at the DRG orDR.

In various embodiments herein, conventional SCS electrodes and leads maybe used for stimulation and/or sensing, provided that the SCS electrodesare configured to be located at a desired proximity relative to a targetsite or nervous tissue of interest. Additionally, or alternatively, thelead to be used for sensing may include micro electrodes (alone or incombination with conventional SCS electrodes), where the microelectrodes that are configured to be placed immediately adjacent fibersof interest, such as C-fibers and/or A-delta fibers.

At 306, the SAP baseline sample is analyzed to define baseline featureswithin the morphology of the SAP signal. For example, the baselinefeatures may represent the frequency of SAP within a certain period oftime window, an amplitude of peaks, a number of peaks, a number ofdirection changes and the like within the SAP baseline sample over thedata collection window. The SAP baseline sample(s) and their featuresdescribed above are stored in memory. The SAP baseline samples may beused over time as a reference for comparison with later collected SAPbaseline samples, such as to determine when a patient's inherent levelof SAP activity is increasing or decreasing. Optionally, the operationsat 304 and 306 may be omitted entirely.

At 308, the method delivers the non-paresthesia stimulation waveform toat least one electrode based on the TPS defined at 302. The stimulationwaveform is delivered to at least one stimulation electrode on the lead.The stimulation waveform may represent a series of monophasic pulses(with a positive or negative current pulse) or a series of biphasicwaveform (with positive and negative pulses). When the stimulationwaveform is biphasic, a first pulse phase may be configured to captureat least a portion of the A-delta fibers and/or C-fibers, while thesecond pulse phase is configured to repolarize charge at a stimulationsite. By repolarizing charge at the stimulation site, the second pulsephase limits an extent of A-delta fiber and/or C-fiber excitation (e.g.,a degree to which, or amount of, the fibers of interest are excited).

At 310, the method applies a predetermined external sensory stimulationas a noxious or reference input that is configured to excite the fibersof interest (e.g. A-delta fibers and/or C-fibers). The reference inputmay represent a predetermined degree or amount of touch, pinch,pressure, application of an external temperature source, or any othernoxious external input intended to otherwise cause activity within thefibers of interest. The reference input is applied in a repeatablemanner such that a common amount of touch, pinch, pressure, externaltemperature and the like may be applied repeatedly at different timeswhile SAP signals are collected in connection with different TPS.

At 312, the method senses SAP signals and collects the SAP signals for adata collection window. The SAP signals are indicative of the sensoryaction potential experienced by nervous tissue of interest at the targetposition in response to the reference or noxious input. The SAP signals,collected over a single data collection window, represent an SAP samplefor a single time interval, where the SAP sample is indicative of aresponsiveness of the fibers of interest (C-fibers and/or A-deltafibers) when a predetermined external sensory stimulation k delivered.For example, the responsiveness may correspond to a predetermined amountof touch, pressure, and external temperature source, or any otherexternal input that would otherwise cause activity within the fibers ofinterest. The SAP signals are saved as an SAP sample.

At 312, the patient also enters a pain score to indicate anamount/degree of pain experienced by the patient relative to apredetermined pain index.

At 314, the method analyzes the SAP signal (e.g., the SAP sample) toobtain activity data associated with the TPS. The activity datacorresponds to activity for the fiber of interest, such as at least oneof the SAP C-fiber components and/or SAP A-delta fiber components. Theanalysis at 314 is repeated numerous times to obtain a collection ofactivity data associated with a group or multiple TPS. In the embodimentillustrated in FIG. 3A, the operation at 314 may be implemented duringeach iteration through the operation at 308-320. Optionally, theoperation at 314 may be implemented once after an entire collection ofactivity data is obtained from a predetermined number of iterationsthrough the operations at 308-320 for the group or multiple differentcombinations of therapy parameters.

At 314, the method also saves the pain score, and activity data alongwith the values for the corresponding therapy parameter set, such as ina memory of the IPG, external programmer or other external device. Theactivity data, pain scores and the associated therapy parameter set aresaved, over time, in connection with delivering therapy based onmultiple therapy parameter sets, thereby developing atherapy/sensitivity history for the patient. The therapy/sensitivityhistory indicates, among other things, a degree to which certaintherapies inhibit sensory action potentials along conduction nervefibers of interest (e.g., the C-fibers and/or A-delta fibers). Thesensing and analyzing operations at 310 and 312 are described in moredetail in connection with FIG. 3B.

At 316, the method determines whether a sufficient number of SAP sampleshave been collected (and analyzed). When a sufficient number of SAPsamples have been collected, flow moves to 322. When it is determinedthat additional SAP samples should be collected, flow moves along 318 to320.

At 320, the method changes a value for one or more of the parameterswithin the therapy parameter set. The change at 320 may be performed ina predetermined systematic stepwise manner. For example, each parameterwithin the therapy parameter set may be incrementally adjusted by aselect amount during separate iterations through the operations at308-316. As an example, during iterations 1-3, the method may onlychange the amplitude of the stimulation waveform between low, medium andhigh amplitudes, while maintaining constant all other parameters withinthe TPS. After cycling through each of the pulse amplitudes of interest,the pulse amplitude may be reset to the low level for iterations 4-6,during which the pulse width is changed from short to medium to long.During iterations 7-9, the pulse amplitude may be set to the mediumlevel, while the pulse width is again changed from short to medium tolong, while all other parameters are maintained constant. The foregoingprocess may be repeated until each, or at least a select portion, of thepotential permutations and combinations of levels for the parameters areused during the operations at 308-316 to form the group of TPS for whichthe collection of activity data is accumulated.

Alternatively, or additionally, not all permutations and combinations ofparameter levels may be used. For example, a physician or other user mayselect (and/or program) individual TPS of interest to be tested as thegroup of TPS. For example, the operations at 308-316 may only berepeated for 5 to 10 or 20 different TPS, even though many morepermutations and combinations of levels for the various parametersexist. The change performed at 320 may be based on pre-stored settingsor may represent an input from a physician or other user duringoperation.

Optionally, the amount of change during each iteration through 320 mayvary, such as with larger step changes made during initial iterationsand smaller step changes made during later iterations. Optionally, theamount of change at 320 may be based on a difference between theactivity data and the threshold. For example, when the activity datasubstantially exceeds the threshold, larger changes may be applied toone or more parameters at 320. As the difference between the activitydata and threshold decreases, the incremental change in the one or moreparameters is changed by similarly/proportionally decreasing amounts.Following 320, flow returns to 308.

The operations at 308-316 build a database, file, or generally apain-activity data relation corresponding to a relation between highfrequency content of the SAP signals and pain scores indicative of alevel of pain experienced by the patient.

At 322, the method selects a candidate TPS from the multiple or group ofTPS based on one or more criteria of interest. For example, when thecriteria of interest represents a threshold or predetermined range forthe activity data, the candidate TPS may be selected as the TPS thatresulted in activity data that satisfy the threshold or predeterminedrange. For example, when the criteria of interest represents sensoryactivity, at 322, the method may identify the SAP sample for which thelowest or smallest amount of activity data was identified. The lowest orsmallest amount of activity is measured relative to the activity data ofthe other SAP samples. The method cross references SAP sample, thatexhibits the lowest or smallest amount of activity data, to thecorresponding therapy parameter set which is designated as the candidateTPS. As one example, the selection at 322 may seek to optimize thecandidate TPS to define as a burst stimulation waveform that affords anSAP activity below a threshold or within a range, collectively referredto as a result of interest, without inducing paresthesia. Once acandidate TPS is selected, the candidate TPS is used for subsequenttherapy for a period of time, for example until it becomes desirable torepeat the process of FIG. 3A to determine a new candidate TPS.

The operations at 308-320 may be repeated for a number of differenttherapy parameter sets. For example, it may be desirable to obtainactivity data in connection with 5, 10 or more than 10 differentstimulation waveforms, in order to derive a more complete understandingof a particular patient's neural fiber activity respond to differentstimulation waveforms. When a sufficient amount of activity data (e.g.enough SAP samples) is collected, the process ends and the candidate TPSis selected and implemented.

The operations at 308-320 are iteratively repeated to form a feedbackloop in which the therapy parameter set is continuously updated untilobtaining a burst stimulation waveform that inhibits spontaneous actionpotentials along the slow conduction fibers to no more than a selectamount of activity.

FIG. 3B illustrates a process for collecting and analyzing SAP signalsto obtain the activity data in connection with the operations 312 and314 of FIG. 3A in accordance with embodiments herein. The operations ofFIG. 3B may be implemented by one or more processors, such as within animplantable pulse generator, and external programmer, an external deviceand the like. The IPG, external programmer or other external device arecoupled to a lead having at least one stimulation electrode that isimplanted at a target position proximate to nervous tissue of interest.

At 352, the method utilizes one or more electrodes on one or more leadsimplanted proximate to the target site to sense SAP signals indicativeof a sensory action potential of the nervous tissue of interest. The SAPsignals are collected over a data collection window (e.g., a fewseconds, a few minutes or otherwise) and saved in memory (e.g., memory158). The SAP signals are sensed between therapies such that nostimulation is delivered while collecting SAP signals. The electrodes atwhich the SAP signals are sensed may be the same as, partially commonwith, or entirely distinct from the electrode or electrodes used todeliver therapy. The electrodes may represent micro-electrodespositioned to directly sense signals from C-fibers. Optionally, theelectrodes may represent electrodes on a conventional SCS lead that arepositioned and configured to sense sensory action potentials fromvarious fibers within the spinal column, such as the A-beta fibers.

At 354, the method determines whether the SAP signal represents a signalthat directly measures the sensory action potential of the conductingfibers of interest, such as C-fibers and/or A-delta fibers. By way ofexample, when micro electrodes are positioned immediately adjacentC-fibers and/or A-delta fibers, the sensed SAP signal would represent adirect measure of the sensory action potential of the slow conductingfibers of interest. Alternatively, when a conventional lead with largerelectrodes are positioned in the dorsal column, the larger electrodesare not positioned immediately adjacent C-fibers and/or A-delta fibers.Instead, the larger electrodes measure a “composite” sensory actionpotential from multiple types of fibers in the dorsal column, where thecomposite SAP includes SAP components associated with fast conductingfibers and SAP components associated with slow conducting fibers. Forexample, the composite SAP signal may include an A-alpha fiber SAPcomponent, A-beta fiber SAP component, an A-delta fiber SAP component, aB-fiber SAP component, a C-fiber SAP component and the like.

At 354, when the method determines whether the sensed SAP signalcorresponds directly to the conduction SAP component of interest (e.g.the C-fiber component and/or A-delta fiber component) and thusrepresents, conduction SAP data of interest, flow moves to 358.Otherwise, when the method determines at 354 that the sensed SAP signalis a composite SAP signal that does not correspond directly to theconduction SAP component of interest, flow moves to 356.

At 356, the method processes the sensed composite SAP signal to identifythe conduction SAP component and generates conduction SAP data ofinterest based thereon. For example, a fast Fourier transform may beapplied to the composite SAP signal to separate the frequency componentstherein. Certain composite frequency components of the sensed compositeSAP signal entirely or primarily are generated by conduction nervefibers of interest (e.g., C-fibers and/or A-delta fibers). Thus, thecomposite SAP signal may be converted to the frequency domain through anFFT conversion to form FFT converted SAP data. The slow conductionfrequency components of interest from the FFT converted SAP data may beisolated, such as through filtering. Next, the conduction frequencycomponents of interest from the FFT converted SAP data may be returnedat 358 as conduction SAP data in the frequency domain. Optionally, theconduction frequency components in the frequency domain may be convertedthrough an inverse fast Fourier transform back to the time domain toform conduction SAP data in the time domain.

At 358, the method analyzes the conduction SAP data of interest (in thetime domain or frequency domain) for one or more features of interest.For example, the feature of interest may represent a number of positiveand negative peaks within the conduction SAP data for a select period oftime. When processing the conduction SAP data in the time domain, theoperation at 358 may include a binning operation, in which theconduction SAP data is segmented into a series of temporal bins. Eachtemporal bin may include one or more occurrences of the feature ofinterest (e.g. spikes or peaks).

At 360, the method counts a number of occurrences of the feature ofinterest (FOI) within each temporal bin. For example, when analyzing theconduction SAP data in the time domain, each temporal bin may correspondto ½-1 second of conduction SAP data. The conduction SAP data exhibits anumber of spikes/peaks within each temporal bin, where the number ofspikes/peaks is indicative of, and proportional to, an amount of sensoryactivity conveyed along the corresponding conduction nervous fibers. Asmore sensory activity is conveyed along the conduction nervous fibers,the number of spikes/peaks within the temporal bins increase.Conversely, as less sensory activity is conveyed along the conductionnervous fibers, the number of spikes/peaks within the temporal binsdecrease.

At 362, the method derives SAP activity level data from the count forthe temporal bins. For example, the SAP activity level data may indicatethat the number of spikes/peaks are within an acceptable upperlimit/range or below an acceptable threshold, thereby indicating that apresent therapy is acceptable. Alternatively, the SAP activity leveldata may indicate that the number of spikes/peaks is not within anacceptable range or exceeds an upper limit/threshold, thereby indicatingthat the present therapy is not achieving a desired affect and warrantsmodification. The SAP activity level data is stored in combination withthe corresponding therapy. Optionally, additional information regardingthe patient's condition may be stored with the SAP activity level data(e.g. heart rate, physical activity level and the like). The SAPactivity level data is used in accordance with embodiments herein toadjust the therapy parameter set used to define therapy.

As a further option, the SAP activity level data may give additionalinformation about a nature (e.g., amount and/or direction) of the changein the sensory activity. For example, the SAP activity level data mayindicate that the conduction SAP data is exhibiting a certain amount ofchange (e.g. percentage) in sensory activity (e.g. a 5% increase overthe past hour, 10% increase over the past day. The amount of change maybe characterized as a “large” or “small” decrease or increase relativeto an average level of activity or otherwise. For example, the methodmay save SAP activity level data over an extended period of time (e.g.several days, several weeks or longer). The SAP activity level data maybe averaged or otherwise statistically analyzed to determine amathematical indicator of certain characteristics of the SAP activitylevel data. For example, the indicator may denote a baseline amount ofsensory activity. The indicator may denote levels of sensory activityassociated with known or periodic behavior where such level ofreactivity are acceptable and do not warrant modification of the coupledtonic/burst therapy.

The operations of FIG. 3B may be repeated throughout operationperiodically based upon inputs from a patient or clinician, periodicallybased upon an operation of the IPG and the like.

FIG. 3C illustrates a process for generating a correlation between painscores that are noted down by a patient and features of SAP recorded bythe IPG (e.g. counts of SAP in each defined time period of window) inconnection with multiple non-paresthesia therapies in accordance withembodiments herein. Initially, an NS system 100 is implanted andnon-paresthesia therapy is delivered as explained hereafter, while thepatient is requested to provide pain scores in connection with painintensity experienced by the patient.

At 370, the method delivers a non-paresthesia stimulation waveform(defined by a present therapy parameter set) to at least one electrode.

At 372, the method senses SAP signals and collects the SAP signals for adata collection window. The SAP signals are indicative of the sensoryaction potential experienced by nerve tissue of interest at the targetposition with or without noxious input (e.g., due solely to inherentpain). At 372, the patient is also requested to enter a pain intensityscore indicative of a level of pain experienced by the patient.

At 374, the method analyzes the SAP signal (e.g., the SAP sample) toobtain SAP activity data associated with the TPS. As explained herein,the analysis of the SAP signal may produce an indication of a highfrequency (HF) content within the SAP sample, where the HF contentcorresponds to electrical activity exhibited by the fibers of interest,such as at least one of the SAP C-fiber components and/or SAP A-deltafiber components.

At 376, the method determines whether a sufficient number of SAP sampleshave been collected (and analyzed). When a sufficient number of SAPsamples have been collected, flow moves to 378. At 378, the methodchanges a value for one or more of the parameters within the therapyparameter set.

At 376, when it is determined that additional SAP samples should becollected, the process of FIG. 3C ends. The operations at 370-378 may berepeated while changing at least one parameter, thereby definingmultiple therapy parameter sets, each set of which is recorded with acorresponding HF content for the SAP signal and patient designated painscore. The process of FIG. 3C generates a patient specific pain-activitydata relation (also referred to as a patient specific PAD relation)defining a function or relation between HF content of the SAP signalsand pain scores designated by the patient. The patient specific PADrelation may be stored in memory of the NS system 100, an externalprogrammer, another external device, or in a database, on a network, andthe like. By way of example, the patient specific PAD relation may beused by an NS system 100 in connection with automatically adjustingtherapy parameters without further input from the patient.

FIG. 3D illustrates a process for selecting a non-paresthesia therapy inaccordance with embodiments herein. Initially, an external programmer isprovided that is used to select therapy parameters to define anon-paresthesia therapy. The external programmer may be used to controlthe NS system 100 that has been implanted. Alternatively, the externalprogrammer may be coupled to and implanted lead, prior to implant of theNS system 100. Alternatively, or additionally, the external programmermay be coupled to a temporary lead not intended for permanent implant.

At 390, the method delivers a non-paresthesia stimulation waveform(defined by a present therapy parameter set) to at least one electrode,either coupled to the external programmer or coupled to the NS system100, under control of the external programmer.

At 392, the method senses SAP signals and collects the SAP signals for adata collection window. At 392, the method analyzes the SAP signal(e.g., the SAP sample) to obtain SAP activity data, such as the HFcontent of the A-delta fiber component and/or C-fiber component of theSAP signal.

At 394, the method determines whether the activity data that apply acriteria of interest. For example, the method may determine whether thehigh frequency content of the SAP signal falls below a threshold orwithin an acceptable range, thereby indicating that no pain or anacceptable low level of pain is experienced by the patient in connectionwith the present therapy parameter set. As one example, the thresholdmay represent a predetermined HF content level set by a physician, aloneor in combination with feedback from the patient.

Alternatively, or in addition, the threshold may be set based on thepatient specific PAD relation. For example, at 394, the method mayaccess the patient specific PAD relation corresponding to the presentpatient and uses the patient specific PAD relation to determine a rangeor threshold for HF content, at which a patient experience no pain or anacceptable low level of pain. At 394, the method may compare the HFcontent identified at 392 to the patient specific PAD relation, toobtain a corresponding pain score. When the corresponding pain scoreassociated with the measured HF content is below a pain threshold orwithin an acceptable pain range, at 394 the method may determine thatthe HF content of the SAP signal is acceptable and that the presenttherapy parameter set should be utilized long-term. Thus, flow moves to398 and the process ends.

Alternatively, at 394, when the method determines that the highfrequency content of the SAP signal exceeds a threshold or acceptablerange, flow moves to 396. At 396, the method changes one or more therapyparameters and flow returns to 390, at which a new non-paresthesiatherapy is delivered in accordance with the new therapy parameters.

The operation at 390-398 are iteratively repeated until the highfrequency content of the measured SAP signal indicates that the presentnon-paresthesia therapy will sufficiently suppressed pain experienced bythe patient. Optionally, the operations at 390-398 may be repeated apredetermined number of times, after which the process terminates and aone of the non-paresthesia therapies is selected that resulted in adesired change in the SAP signal (e.g. the lowest high frequencycontent).

FIGS. 5A-5D illustrate examples of sensory action potential signalscollected in accordance with embodiments herein. In FIGS. 5A-5D, thevertical axis corresponding to the measured voltage potential, and thehorizontal axis corresponding to time. FIGS. 5A-5D illustrate examplesof potential SAP signals 502, 504, 506 and 508 that may be collected inconnection with delivery of burst stimulation waveforms defined bydifferent therapy parameter sets. The SAP signals 502-508 include SAPsample windows separated by therapy delivery windows. With respect tothe SAP signal 502, first and second SAP sample windows 510, 514 areillustrated to be separated by a burst therapy delivery window 528. WhenSAP signal 502 is collected in the SAP sample windows 510 and 514, notherapy is delivered. When the burst therapy is delivered during thetherapy delivery window 528, the SAP signal 502 is not collected.Similarly, the SAP signals 504-508 include SAP sample windows 516-526,and therapy delivery windows 530-534. The SAP signal is collected insuch a way due to the pacing spike from IPG overlapping with SAP signalsin time windows 528, 530, 532 and 534, and the adjacent following SAPsignals are taken as the SAP associated with each burst stimulationsetting in order to be able to analyze the high component of SAPsignals, rather than pacing spikes.

In another embodiment, when the pacing spike or artifact from the IPG isblanked appropriately so that no stimulation spike could interrupt thecounting of SAP, the SAP signals can be collected for two or more timeperiods in collection windows with and without burst stimulation.

The burst stimulation waveform included fixed parameters of 7 pulsesburst, pulse frequency of 500 Hz, burst frequency of 40 Hz and anamplitude of 90% of the motor threshold for all of SAP signals 502-508.In connection with the SAP signal 502, the burst stimulation waveformwas delivered during the therapy delivery window 528, wherein a pulsewidth of 250 μs is used (as one of the therapy parameters) for eachpulse. In connection with the SAP signal 504, a pulse width of 500 μswas used for each pulse of the burst stimulation waveform deliveredduring the burst therapy delivery window 530. Pulse widths of 750 μs and1000 μs were used for the burst stimulation waveforms delivered duringthe burst therapy delivery windows 532 and 534, respectively, inconnection with SAP signals 506 and 508.

Before, during an initial portion, or throughout data collection duringthe SAP sample windows 510, 514, a reference noxious input is applied toone or more predetermined areas of the patient. For example, the patientmay be pinched, have a hot/cold source applied, scratched or otherwisereceive an external input intended to evoke a sensory response. Thereference noxious input may be applied to one or more areas on one ormore limbs of the patient.

FIGS. 5A-5D also illustrate SAP activity data 540-546 that is obtainedwhen the SAP signals 502-508, respectively, are analyzed. The activitydata 540-546 is divided into activity data segments 548-562. Forexample, the activity data 540 includes first and second SAP activitydata segments 548 and 550. The first activity data segment 548 may alsobe referred to as a pre-therapy SAP activity data segment 548, as theSAP sample window 510 occurs before delivery of the burst stimulationwaveform during window 528. The second activity data segment 550 mayalso be referred to as a post therapy activity data segment 550, as theSAP sample window 514 occurs after delivery the burst stimulationwaveform during window 528. The activity data 542-546 are alsopartitioned into pre-therapy activity data segments 552, 556 and 560,and post therapy activity data segments 554, 558 and 562.

The pre-and post-therapy SAP activity data segments 548-562 are dividedinto temporal bins 568, each bin of which corresponds to a temporalportion of the SAP signals 502-508. The data segments 548-562 includecounts 564 of the number of peaks or spikes in the corresponding SAPsignal 502-508 for the corresponding temporal bin 568. The counts 564correspond to the number of neuronal firing evoked by the noxious input(e.g., a pinch of a forearm).

The data segments 552, 556 and 560 exhibit high counts 564 within amajority of the bins 568, as compared to the data segments 554, 558 and562 which exhibit lower count 564 within a majority of the bins 568. Thefrequency/count 564 may be summed for each single data segment 548-562and compared to the related data segment (e.g., data segment 548compared to 550) to determine a change in activity. By way of example,the sum of the count 564 of spikes in the post therapy data segment 554(corresponding to the SAP sample window 518) exhibits a 15% decrease inthe count of spikes, as compared to the sum of the count of spikes inthe pre-therapy data segment 552 (corresponding to the SAP sample window516). The sum of the count 564 of spikes in the post therapy datasegment 558 (corresponding to the SAP sample window 522) exhibits a 24%decrease in the count of spikes, as compared to the sum of the count ofspikes in the pre-therapy data segment 556 (corresponding to the SAPsample window 520). The sum of the count 564 of spikes in the posttherapy data segment 562 (corresponding to the SAP sample window 526)exhibits a 49% decrease in the count of spikes. as compared to the sumof the count of spikes in the pre-therapy data segment 560(corresponding to the SAP sample window 524).

When the counts 564 in the activity data segments 552, 556 and 560 arecompared to the counts 564 in the activity data segments 554, 558 and562, it is seen that the sensory action potential (as measured in theSAP signals 504-508) was reduced/attenuated after delivery of the burststimulation waveforms to varying degrees. The degree to which thesensory action potential was attenuated is dependent, at least in part,on the burst therapy parameters. When no burst stimulation waveforms aredelivered, the frequency content of the sensory action potentialmeasured over the A-delta and C-fibers is higher. After delivery of aburst stimulation waveform, the sensory action potentials aresuppressed, and the frequency content of SAP decreased. As explainedherein, methods and systems are provided to determine and controltherapy parameter sets for burst and/or high frequency stimulationwaveforms based on dosed bop sensory measurement.

FIG. 6 illustrates a functional block diagram of an embodiment of anelectronic control unit (ECU) 700 that is operated in accordance withthe processes described herein to analyze SAP signals and to interfacewith one or more IPGs and/or leads with electrodes positioned atstimulation sites to deliver coupled tonic/burst therapies and/or sensesensory action potential signals. The ECU 700 may be a workstation, aportable computer, a PDA, a cell phone and the like. The ECU 700includes an internal bus that connects/interfaces with a CentralProcessing Unit (CPU) 702, ROM 704, RAM 706, a hard drive 708, thespeaker 710, a printer 712, a CD-ROM drive 714, a floppy drive 716, aparallel 110 circuit 718, a serial I/O circuit 720, the display 722, atouch screen 724, a standard keyboard connection 726, custom keys 728,and a telemetry subsystem 730. The internal bus is an address/data busthat transfers information between the various components describedherein. The hard drive 708 may store operational programs as well asdata, such as waveform templates and detection thresholds.

The CPU 702 typically includes a microprocessor, a micro-controller, orequivalent control circuitry, and may interface with an IPG and/or lead.The CPU 702 may include RAM or ROM memory, logic and timing circuitry,state machine circuitry, and I/O circuitry to interface with the IPGand/or lead. The display 722 (e.g., may be connected to the videodisplay 732). The touch screen 724 may display graphic informationrelating to the CNS 110. The display 722 displays various informationrelated to the processes described herein. The touch screen 724 acceptsa user's touch input 734 when selections are made. The keyboard 726(e.g., a typewriter keyboard 736) allows the user to enter data to thedisplayed fields, as well as interface with the telemetry subsystem 730.Furthermore, custom keys 728 turn on/off 738 (e.g., EVVI) the ECU 700.The printer 712 prints copies of reports 740 for a physician to reviewor to be placed in a patient file, and speaker 710 provides an audiblewarning (e.g., sounds and tones 742) to the user. The parallel I/Ocircuit 718 interfaces with a parallel port 744. The serial I/O circuit720 interfaces with a serial port 746. The floppy drive 716 acceptsdiskettes 748. Optionally, the floppy drive 716 may include a USB portor other interface capable of communicating with a USB device such as amemory stick. The CD-ROM drive 714 accepts CD ROMs 750.

The CPU 702 is configured to analyze SAP signals collected by one ormore electrodes. The CPU 702 includes a therapy circuit module 764 thatis configured to control delivery of a first current pulse configured asa tonic stimulation waveform to the at least one electrode. The tonicstimulation waveform is configured to excite A-beta fibers of thenervous tissue. The therapy circuit module 764 is further configured to,after a tonic-burst delay, control delivery of second current pulsesconfigured as a burst stimulation waveform to at least one electrode.The burst stimulation waveform is configured to excite C-fibers of thenervous tissue.

The CPU 702 also includes a delay adjustment circuit module 762 thatadjusts the tonic-burst delay between the tonic and burst stimulationwaveforms to deliver the burst stimulation waveform during a refractoryperiod of the A-beta fibers excited by the tonic stimulation waveform toavoid excitation of the A-beta fibers excited by the tonic stimulationwaveform, as explained herein. For example, the delay adjustment circuitmodule 762 may adjust the tonic-burst delay to reduce the C-fiber SAPcomponent

The CPU 702 also includes an SAP analysis circuit module 768 thatreceives sensed SAP signals from at least one electrode on the lead andanalyzes the SAP signals to identify a C-fiber sensory action potential(C-fiber SAP) component of the signals. For example, the SAP analysiscircuit module 768 may determine an amount to adjust the tonic-burstdelay based on the C-fiber SAP component of the signals. The SAPanalysis circuit module 768 may adjust analyze a feature of interestfrom a morphology of the C-fiber SAP component over time, count a numberof occurrences of the feature of interest that occur within the C-fiberSAP component over a predetermined duration, compare the number ofoccurrences to a prior number of occurrences, and determine and amountto adjust the tonic-burst delay based on the comparing operation. TheSAP analysis circuit module 768 may analyze the C-fiber SAP component todetermine SAP activity level data for a present/current coupledtonic/burst therapy. The SAP activity level data is saved in memory withthe associated therapy parameters.

In accordance with at least one embodiment, SAP activity level data iscollected in connection with a plurality of coupled tonic-bursttherapies. The SAP activity levels are compared and a select one of theSAP activity levels is chosen. For example, a lowest SAP activity levelmay be chosen. Alternatively, a most frequent SAP activity level may bechosen. Alternatively, a lowest or most frequent SAP activity levelwithin a select range or below an upper limit may be chosen. A coupledtonic-burst therapy associated with the chosen SAP activity level isidentified from the therapies stored in memory. The delay adjustmentcircuit module 762 adjusts the tonic-burst delay to correspond to theidentified coupled tonic-burst therapy.

The telemetry subsystem 730 includes a central processing unit (CPU) 752in electrical communication with a telemetry circuit 754, whichcommunicates with both an SAP circuit 756 and an analog out circuit 758.The circuit 756 may be connected to leads 760. The circuit 756 may alsobe connected to implantable leads to receive and process SAP signals.Optionally, the SAP signals sensed by the leads may be collected by theCNS 110 and then transmitted, to the ECU 700, wirelessly to thetelemetry subsystem 730 input.

The telemetry circuit 754 is connected to a telemetry wand 761. Theanalog out circuit 758 includes communication circuits to communicatewith analog outputs 763. The ECU 700 may wirelessly communicate with theCNS 110 and utilize protocols, such as Bluetooth, GSM, infrared wirelessLANs, HIPERLAN, 3G, satellite, as well as circuit and packet dataprotocols, and the like. Alternatively, a hard-wired connection may beused to connect the ECU 700 to the CNS 110.

One or more of the operations described above in connection with themethods may be performed using one or more processors. The differentdevices in the systems described herein may represent one or moreprocessors, and two or more of these devices may include at least one ofthe same processors. In one embodiment, the operations described hereinmay represent actions performed when one or more processors (e.g., ofthe devices described herein) are hardwired to perform the methods orportions of the methods described herein, and/or when the processors(e.g., of the devices described herein) operate according to one or moresoftware programs that are written by one or more persons of ordinaryskill in the art to perform the operations described in connection withthe methods.

The controller 160 may include any processor-based ormicroprocessor-based system including systems using microcontrollers,reduced instruction set computers (RISC), application specificintegrated circuits (ASICs), field-programmable gate arrays (FPGAs),logic circuits, and any other circuit or processor capable of executingthe functions described herein. Additionally, or alternatively, thecontrollers 151, 206, 1006 and the controller device 160 may representcircuit modules that may be implemented as hardware with associatedinstructions (for example, software stored on a tangible andnon-transitory computer readable storage medium, such as a computer harddrive, ROM, RAM, or the like) that perform the operations describedherein. The above examples are exemplary only and are thus not intendedto limit in any way the definition and/or meaning of the term“controller.” The controllers and the controller device may execute aset of instructions that are stored in one or more storage elements, inorder to process data. The storage elements may also store data or otherinformation as desired or needed. The storage element may be in the formof an information source or a physical memory element within thecontrollers and the controller device. The set of instructions mayinclude various commands that Instruct the controllers and thecontroller device to perform specific operations such as the methods andprocesses of the various embodiments of the subject matter describedherein. The set of instructions may be in the form of a softwareprogram. The software may be in various forms such as system software orapplication software. Further, the software may be in the form of acollection of separate programs or modules, a program module within alarger program or a portion of a program module. The software also mayinclude modular programming in the form of object-oriented programming.The processing of input data by the processing machine may be inresponse to user commands, or in response to results of previousprocessing, or in response to a request made by another processingmachine.

It is to be understood that the subject matter described herein is notlimited in its application to the details of construction and thearrangement of components set forth in the description herein orillustrated in the drawings hereof. The subject matter described hereinis capable of other embodiments and of being practiced or of beingcarried out in various ways. Also, it is to he understood that thephraseology and terminology used herein is for the purpose ofdescription and should not be regarded as limiting. The use of“including,” “comprising,” or “having” and variations thereof herein ismeant to encompass the items listed thereafter and equivalents thereofas well as additional items.

It is to be understood that the above description is intended to beillustrative, and not restrictive. For example, the above-describedembodiments (and/or aspects thereof) may be used in combination witheach other. In addition, many modifications may be made to adapt aparticular situation or material to the teachings of the inventionwithout departing from its scope. While the dimensions, types ofmaterials and coatings described herein are intended to define theparameters of the invention, they are by no means limiting and areexemplary embodiments. Many other embodiments will be apparent to thoseof skill in the art upon reviewing the above description. The scope ofthe invention should, therefore, be determined with reference to theappended claims, along with the full scope of equivalents to which suchclaims are entitled. In the appended claims, the terms “including” and“in which” are used as the plain-English equivalents of the respectiveterms “comprising” and “wherein.” Moreover, in the following claims, theterms “first,” “second,” and “third,” etc. are used merely as labels,and are not intended to impose numerical requirements on their objects.Further, the limitations of the following claims are not written inmeans-plus-function format and are not intended to be interpreted basedon 35 U.S.C. § 112(f), unless and until such claim limitations expresslyuse the phrase “means for” followed by a statement of function void offurther structure.

1. A method to treat chronic pain in a patient by controllingnon-paresthesia stimulation of neural tissue of a dorsal root ganglionof the patient, the method comprising: providing a lead having at leastone electrode on the lead configured to be implanted at a targetposition proximate to neural tissue of the dorsal root ganglion of thepatient; delivering a non-paresthesia stimulation waveform to the atleast one electrode based on a therapy parameter set (TPS), thestimulation waveform including a series of pulses configured to exciteat least one of A-delta fibers or C-fibers of the neural tissue of thedorsal root ganglion of the patient; sensing sensory action potential(SAP) signals; iteratively repeating the delivering and sensingoperations while changing t least one parameter from the TPS; applying areference input during an interval between successive burst waveforms ofthe non-paresthesia stimulation waveform, the reference input creatingthe SAP signals sensed; analyzing the SAP signals to obtain SAP activitydata associated with the TPS for at least one of an SAP C-fibercomponent or an SAP A-delta fiber component, the analyzing operationsobtaining a collection of SAP activity data associated with multipletherapy parameter set; selecting one or more parameters for the TPSbased on the collection of SAP activity data; programming an implantablepulse generator to deliver stimulation to neural tissue of the dorsalroot ganglion according to the TPS; and activating the implantable pulsegenerator to deliver electrical stimulation to the patient according tothe programmed TPS.